'Good' Bacteria Ease Autism-like Behaviors in Mouse Model

In mice, infection or inflammation during pregnancy can produce offspring with autism-like behaviors such as social avoidance, anxiety and repetitive behaviors. In a new study, researchers reduced these behaviors by feeding the mice bacteria found in a healthy human gut. The research adds to growing evidence of a gut-brain connection in autism spectrum disorder (ASD). It appears today in the journal Cell.

"There's likely a lot going on outside the brain in some individuals with ASD," comments Autism Speaks Chief Science Officer Rob Ring. “Studies that improve our understanding of these brain-gut connections are laying a pathway to innovations in treatment for those who want or need it."

Autism Speaks supported the research with a Weatherstone Predoctoral Fellowship for lead researcher Elaine Hsiao and a Suzanne and Bob Wright Trailblazer Award for senior researchers Paul Patterson and Sarkis Mazmanian, all of the California Institute of Technology.  

“These findings represent a breakthrough in understanding the link between the gut and brain in ASD,” says Paul Wang, Autism Speaks vice president for medical research. “Previous research gave us tantalizing clues about autism-related differences in the gut microbiome. These new results tell us that we need to invest in further study of GI-related treatments.” 

In their study, the researchers used the maternal immune activation (MIA) mouse model of autism. These mice are born to mothers exposed to viral infection during pregnancy and display autism-like behaviors. Similar links between autism and prenatal infection or inflammation have been documented in people. 

In the current study, the researchers showed that MIA mice have altered intestinal bacteria and other gut abnormalities. These included defects in the barrier between the gut and bloodstream. Such a "leaky gut" can trigger inflammation when bacteria or other intestinal contents stray into the blood.

Indeed, the MIA mice had high levels of microbial byproducts in their blood. When the researchers administered these byproducts to otherwise normal mice, they too began showing autism-like behaviors.

In the treatment stage of their study, the researchers fed the MIA mice Bacteroides fragilis, a microbe abundant in a healthy human intestinal tract. This significantly reduced the mice's autism-like behaviors as well as the leakiness of their guts.

“Taken together, the findings provide strong support of a gut-brain connection in this mouse model of autism,” Dr. Wang comments. Caution is needed in applying the results to people, he adds. “We need further study to determine possible benefits of probiotic therapy in persons with autism.” Based on their findings, the Caltech researchers are working with collaborators to evaluate such a probiotic treatment in clinical trials.